In medical devices such as catheters, catheter inducers, guidewires and the like, it is often desirable to coat various plastic, rubber or metal parts thereof with products made from hydrophilic or certain other polymers that are lubricious and which produce low coefficients of friction during use. However, one of the problems associated with the utility of such coatings is their inability to remain intact and abrasion-resistant during clinical use in body fluids such as blood. Catheters used in angioplasty, gastroenterology and other medical specialties, are commonly made of polymeric materials which most often are relatively hydrophobic and not inherently slippery or biocompatible. Metal devices and components, such as guidewires to which permanent adhesion of slip agents and/or hydrophilic polymers is often desired, present additional challenges. In any case, polymeric and metallic substrates generally require some surface modification in order to reduce the friction between the catheter and other devices with which they work, such as vascular sheaths, and also to reduce the friction between the vasculature or other anatomical passageways and the catheter itself. Almost all currently used catheters have some form of surface modification or coating applied to them. The ability of the coating to reduce frictional resistance, its durability, as well as its biocompatibility are the most important functional aspects of an effectively coated surface.
It has been recognized that polymer surfaces can be provided with hydrophilic coatings formed by the combinations of certain polymers, both non-cross-linked and cross-linked, with a hydrophilic polymer like polyvinylpyrrolidone (PVP) or poly(ethylene oxide) (PEO). For example, U.S. Pat. Nos. 5,077,352, 5,160,790, 5,179,174 and 5,290,585 to ELTON each disclose a flexible, lubricious organic coating formed by applying a mixture of an isocyanate, a polyol, a hydrophilic polymer like poly(ethylene oxide) (PEO) or polyvinylpyrrolidone (PVP) and a carrier liquid to a surface to be coated. The carrier liquid is removed and the mixture reacted to form a lubricous, flexible homogenous coating of crosslinked polyurethane linkages complexed with PVP or PEO particularly suitable for use as a protective lubricous coating on medical devices introduced into the body.
The use of a crosslinked polyurethane complexed with poly(ethylene oxide) (PEO) or polyvinylpyrrolidone (PVP) has proven to be an effective, lubricous and durable coating on numerous organic substrates. However, there are several organic substrates and numerous inorganic and organometallic substrates (glass, ceramic, metal, silicone, etc.) that first require surface treatment/modification to provide an effective lubricous, durable coating when aforementioned polyurethane complexed with PEO or PVP coatings are applied.
The crosslinked polyurea/PEO or PVP coatings are generally formed from the curing of the product resulting from the reaction of an isocyanate and a compound having at least two active hydrogens per molecule selected from the group consisting of polyamines, polymercaptans, and polycarboxylates or compounds with NH, NH2, SH or COOH groups on the same molecule, in the presence of the hydrophilic PEO or PVP polymer.
Polymers such as butyl rubber are commercial elastomers with many desirable properties including high elasticity, impermeability to gas and water, damping characteristics, and chemical stability. However, due to its nonpolar nature, evidenced by its relatively high surface contact angle of approximately 90°, it is widely recognized to have poor compatibility with more polar polymers and materials. In particular, spreading of more hydrophilic materials on the polymer surface during a coating process is not easily achieved in a uniform manner. The incompatibility between two different materials with two different properties, hydrophilic and hydrophobic can create partial or complete dewetting after casting of the coating. Consequently, the obtained non-homogeneous layer is not suitable for physical grafting using processes such as plasmas or hyperthermal hydrogen induced cross-linking (HHIC). The resulting surfaces are not suitable for high end applications such as biomedical, where a high degree of control over the surface and its uniformity is required.
There are many examples describing the use of hydrophilic polymers (such as PEO) coated surfaces to resist the adsorption of protein. Many of these examples involve the chemical attachment of functionalized hydrophilic polymers to the surface. These methods cannot be applied directly to polymer surfaces that do not inherently have reactive chemical functionalities. For example, butyl rubber, which is composed almost entirely of C—C, and C—H bonds with only a small percentage of C═C bonds from the isoprene units. Physical treatments such as plasma or electron beam can be used, but they generally require the coating of the surface with the hydrophilic polymers such as PEO. The incompatibility of hydrophobic or non-polar or less polar polymer surfaces with hydrophilic or more polar polymers, results in poor wetting. Therefore, for use of these physical treatment methods, it is important to resolve the wettability problem.
Haldar and Singha (J. Appl. Polym. Sci. 2006, 101, 1340-1346) have described the grafting of butyl acrylate and methyl methacrylate on butyl rubber surfaces using electron beam radiation (i.e., polymerization from the surface) as a means to potentially enhance compatibility of butyl with other polymers. No compatibility properties were investigated and based on their microscopy images, their layers of PMMA deposited on the surface do not appear to be uniform.
U.S. Patent Publication Nos. 2002/0028883 A1 and 2003/0096911 A1 describe the production of compatibilized blends of general purpose rubbers and benzyl halide polymers through the solventless reaction of a multifunctional reagent that reacts with the benzylic halide in one polymer and the diene in the other polymer. U.S. Patent Publication No. 2008/0214669 A1 also discloses a similar approach. These approaches are aimed at the bulk blending of materials, and involve specific chemical reactions between the two polymers. U.S. Pat. No. 5,352,739 describes a process for compatibilizing polar/nonpolar rubber blends using compatibilizer additives such as ethylene/vinyl acetate or ethylene/methacrylate copolymers. There are many other examples of compatibilization methods for the blending of bulk materials.
U.S. Pat. No. 6,270,902 describes a method for improving the adherence or bonding of lubricious coatings including PEO on a variety of surfaces, including mention of commercial rubbers. This method involves a 2-step process where the first step is the high energy treatment such as plasma, or corona and electron discharges to etch the surface and deposit reactive functional groups. The next step involves the chemical reaction of these functional groups with a suitable functionalized PEO derivative. The method disclosed in this patent is based on specific chemical reactions between the layers. This patent, however, does not provide any data on protein adsorption or cell growth on the coated polymer surfaces discloses therein.